PMID- 34882826 OWN - NLM STAT- MEDLINE DCOM- 20220414 LR - 20220414 IS - 1875-9114 (Electronic) IS - 0277-0008 (Linking) VI - 42 IP - 2 DP - 2022 Feb TI - Dexmedetomidine for prevention of opioid/benzodiazepine withdrawal syndrome in pediatric intensive care unit: Interim analysis of a randomized controlled trial. PG - 145-153 LID - 10.1002/phar.2654 [doi] AB - STUDY OBJECTIVE: Withdrawal syndrome (WS) may be a critical drawback of opioid/benzodiazepine weaning in children. The most effective intervention to reduce WS prevalence is yet to be determined. Dexmedetomidine (DEX) was estimated to be effective in reducing WS-related symptoms, but no randomized trial has been conducted to prove its efficacy so far. We aimed to evaluate the efficacy and safety of DEX in reducing the occurrence of WS. DESIGN AND SETTING: This was an adaptive randomized double-blind placebo-controlled trial conducted at three Italian Pediatric Intensive Care Units (PICUs). PATIENTS: It included children admitted to PICU, undergoing at least five days of opioids/benzodiazepines continuous infusion, and ready to start the analgosedation weaning. INTERVENTION: Twenty-four hours before the start of weaning, an infusion of DEX/placebo was started. WS symptoms were monitored using the Withdrawal-Assessment-Tool-version-1 (WAT-1). In case of WS symptoms (WAT-1 >/= 3) an opioid/benzodiazepine bolus was given and the DEX/placebo infusion-rate was increased. MEASUREMENTS: The primary outcome measure was the prevalence of WS. Secondary outcomes were the trend of WAT-1 over time, number of rescue doses, length of weaning and PICU-stay, and onset of adverse events (AEs). MAIN RESULTS: Forty-five patients were enrolled, of whom 5 dropped-out and 40 entered the interim analysis. There were no significant baseline differences between groups. WS prevalence did not significantly differ between groups (77.8% DEX vs 90.9% placebo, p = 0.381). By generalized linear mixed modeling, the WAT-1 trend showed a significant increase per unit of time in the DEX arm (estimate 0.27, CI 0.07-0.47, p = 0.009) compared to placebo. Most frequent AEs were hemodynamic, and all of them happened in the DEX arm. CONCLUSIONS: A continuous infusion of DEX, started 24 h before the analgosedation weaning and increased based on WS signs, was not able to significantly modify the prevalence of WS in children who received at least five days of opioids/benzodiazepines treatment compared to placebo. CI - (c) 2021 Pharmacotherapy Publications, Inc. FAU - Mondardini, Maria Cristina AU - Mondardini MC AUID- ORCID: 0000-0002-8398-3166 AD - Pediatric Anesthesia and Intensive Care Unit, Department of Woman's and Child's Health, University Hospital of Bologna IRCCS S. Orsola Polyclinic, Bologna, Italy. FAU - Daverio, Marco AU - Daverio M AD - Pediatric Intensive Care Unit, Department of Woman's and Child's Health, University-Hospital, Padua, Italy. FAU - Caramelli, Fabio AU - Caramelli F AD - Pediatric Anesthesia and Intensive Care Unit, Department of Woman's and Child's Health, University Hospital of Bologna IRCCS S. Orsola Polyclinic, Bologna, Italy. FAU - Conti, Giorgio AU - Conti G AD - Pediatric Intensive Care Unit and Pediatric Trauma Center, Department of Anesthesia and Intensive Care, Catholic University of Rome, A Gemelli Polyclinic, Rome, Italy. FAU - Zaggia, Cristina AU - Zaggia C AD - Pediatric Intensive Care Unit, Department of Woman's and Child's Health, University-Hospital, Padua, Italy. FAU - Lazzarini, Rossella AU - Lazzarini R AD - Pediatric Anesthesia and Intensive Care Unit, Department of Woman's and Child's Health, University Hospital of Bologna IRCCS S. Orsola Polyclinic, Bologna, Italy. FAU - Muscheri, Lidia AU - Muscheri L AD - Pediatric Intensive Care Unit and Pediatric Trauma Center, Department of Anesthesia and Intensive Care, Catholic University of Rome, A Gemelli Polyclinic, Rome, Italy. FAU - Azzolina, Danila AU - Azzolina D AD - Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University-Hospital of Padua, Padua, Italy. FAU - Gregori, Dario AU - Gregori D AD - Unit of Biostatistics, Epidemiology and Public Health, Department of Cardiac, Thoracic, Vascular Sciences and Public Health, University-Hospital of Padua, Padua, Italy. FAU - Sperotto, Francesca AU - Sperotto F AD - Pediatric Intensive Care Unit, Department of Woman's and Child's Health, University-Hospital, Padua, Italy. AD - Department of Cardiology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA. FAU - Amigoni, Angela AU - Amigoni A AD - Pediatric Intensive Care Unit, Department of Woman's and Child's Health, University-Hospital, Padua, Italy. LA - eng SI - ClinicalTrials.gov/NCT03645603 SI - EudraCT/2015-002114-80 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20211221 PL - United States TA - Pharmacotherapy JT - Pharmacotherapy JID - 8111305 RN - 0 (Analgesics, Opioid) RN - 0 (Hypnotics and Sedatives) RN - 12794-10-4 (Benzodiazepines) RN - 67VB76HONO (Dexmedetomidine) SB - IM MH - Analgesics, Opioid MH - Benzodiazepines/therapeutic use MH - Child MH - *Dexmedetomidine/adverse effects MH - Humans MH - Hypnotics and Sedatives/adverse effects MH - Intensive Care Units, Pediatric MH - *Substance Withdrawal Syndrome/drug therapy/epidemiology/prevention & control OTO - NOTNLM OT - benzodiazepine OT - dexmedetomidine OT - intensive care unit OT - opioid OT - pediatric OT - sedation OT - withdrawal syndrome EDAT- 2021/12/10 06:00 MHDA- 2022/04/15 06:00 CRDT- 2021/12/09 17:39 PHST- 2021/11/07 00:00 [revised] PHST- 2021/09/19 00:00 [received] PHST- 2021/11/10 00:00 [accepted] PHST- 2021/12/10 06:00 [pubmed] PHST- 2022/04/15 06:00 [medline] PHST- 2021/12/09 17:39 [entrez] AID - 10.1002/phar.2654 [doi] PST - ppublish SO - Pharmacotherapy. 2022 Feb;42(2):145-153. doi: 10.1002/phar.2654. Epub 2021 Dec 21.